This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded pro... See more...

Aliases for SESN1 Gene

Aliases for SESN1 Gene

  • Sestrin 1 2 3 5
  • SEST1 2 3 4
  • PA26 2 3 4
  • Sestrin-1 3 4
  • P53 Regulated PA26 Nuclear Protein 3
  • P53-Regulated Protein PA26 4
  • P53 Activated Gene 26 3
  • EC 1.11.1.- 4
  • SESN1 5

External Ids for SESN1 Gene

Previous GeneCards Identifiers for SESN1 Gene

  • GC06M109307
  • GC06M109353
  • GC06M109414
  • GC06M106874

Summaries for SESN1 Gene

Entrez Gene Summary for SESN1 Gene

  • This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

GeneCards Summary for SESN1 Gene

SESN1 (Sestrin 1) is a Protein Coding gene. Diseases associated with SESN1 include Endometrial Adenosquamous Carcinoma and Tuberous Sclerosis 2. Among its related pathways are DNA Damage Response and Gene Expression. An important paralog of this gene is SESN3.

UniProtKB/Swiss-Prot Summary for SESN1 Gene

  • Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:25263562, PubMed:26449471). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May have an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (By similarity).

Gene Wiki entry for SESN1 Gene

Additional gene information for SESN1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SESN1 Gene

Genomics for SESN1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SESN1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SESN1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SESN1

Top Transcription factor binding sites by QIAGEN in the SESN1 gene promoter:
  • FOXO4
  • Pax-4a
  • Pax-5
  • POU2F1a
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • Sox5
  • Sp1

Genomic Locations for SESN1 Gene

Genomic Locations for SESN1 Gene
chr6:108,984,309-109,094,846
(GRCh38/hg38)
Size:
110,538 bases
Orientation:
Minus strand
chr6:109,307,640-109,416,022
(GRCh37/hg19)
Size:
108,383 bases
Orientation:
Minus strand

Genomic View for SESN1 Gene

Genes around SESN1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SESN1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SESN1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SESN1 Gene

Proteins for SESN1 Gene

  • Protein details for SESN1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6P5-SESN1_HUMAN
    Recommended name:
    Sestrin-1
    Protein Accession:
    Q9Y6P5
    Secondary Accessions:
    • Q2M2B7
    • Q5T316
    • Q9NV00
    • Q9UPD5
    • Q9Y6P6

    Protein attributes for SESN1 Gene

    Size:
    492 amino acids
    Molecular mass:
    56557 Da
    Quaternary structure:
    • Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (PubMed:25263562, PubMed:26449471). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). Interacts with KEAP1, RBX1 and SQSTM1; in the SQSTM1-dependent autophagic degradation of KEAP1 (PubMed:23274085). May interact with PRDX1 (PubMed:15105503).

    Alternative splice isoforms for SESN1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SESN1 Gene

Post-translational modifications for SESN1 Gene

  • Ubiquitination at Lys337
  • Modification sites at PhosphoSitePlus

Other Protein References for SESN1 Gene

Antibody Products

  • Abcam antibodies for SESN1
  • Santa Cruz Biotechnology (SCBT) Antibodies for SESN1

No data available for DME Specific Peptides for SESN1 Gene

Domains & Families for SESN1 Gene

Gene Families for SESN1 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for SESN1 Gene

InterPro:
Blocks:
  • PA26 p53-induced protein (sestrin)
ProtoNet:

Suggested Antigen Peptide Sequences for SESN1 Gene

GenScript: Design optimal peptide antigens:
  • p53-regulated protein PA26 (SESN1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y6P5

UniProtKB/Swiss-Prot:

SESN1_HUMAN :
  • Composed of an N-terminal domain that has an alkylhydroperoxide reductase activity and a C-terminal domain that mediates interaction with GATOR2 through which it regulates TORC1 signaling.
  • Belongs to the sestrin family.
Domain:
  • Composed of an N-terminal domain that has an alkylhydroperoxide reductase activity and a C-terminal domain that mediates interaction with GATOR2 through which it regulates TORC1 signaling.
Family:
  • Belongs to the sestrin family.
genes like me logo Genes that share domains with SESN1: view

Function for SESN1 Gene

Molecular function for SESN1 Gene

UniProtKB/Swiss-Prot Function:
Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:25263562, PubMed:26449471). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May have an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[protein]-dithiol + a hydroperoxide = [protein]-disulfide + an alcohol + H2O; Xref=Rhea:RHEA:10008, Rhea:RHEA-COMP:10593, Rhea:RHEA-COMP:10594, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, ChEBI:CHEBI:50058; Evidence={ECO:0000250|UniProtKB:P58004};.
UniProtKB/Swiss-Prot Induction:
Isoform T2 and isoform T3 are induced by genotoxic stress (UV, gamma-irradiation and cytotoxic drugs) in a p53/TP53-dependent manner. Isoform T1 is not induced by p53/TP53.

Enzyme Numbers (IUBMB) for SESN1 Gene

Phenotypes From GWAS Catalog for SESN1 Gene

Gene Ontology (GO) - Molecular Function for SESN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15105503
GO:0016491 oxidoreductase activity IEA --
GO:0016684 oxidoreductase activity, acting on peroxide as acceptor IBA 21873635
GO:0051920 peroxiredoxin activity IEA --
GO:0070728 leucine binding IDA 26449471
genes like me logo Genes that share ontologies with SESN1: view
genes like me logo Genes that share phenotypes with SESN1: view

Animal Models for SESN1 Gene

MGI Knock Outs for SESN1:
  • Sesn1 Sesn1<tm1a(EUCOMM)Wtsi>
  • Sesn1 Sesn1<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for SESN1 Gene

miRTarBase miRNAs that target SESN1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SESN1

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SESN1 Gene

Localization for SESN1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SESN1 Gene

Nucleus. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SESN1 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
mitochondrion 2
endoplasmic reticulum 2
lysosome 2
cytoskeleton 1
peroxisome 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoli fibrillar center (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SESN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001650 fibrillar center IDA --
GO:0005634 nucleus IDA 9926927
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA,IDA 15105503
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with SESN1: view

Pathways & Interactions for SESN1 Gene

genes like me logo Genes that share pathways with SESN1: view

Gene Ontology (GO) - Biological Process for SESN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016239 positive regulation of macroautophagy IBA 21873635
GO:0034198 cellular response to amino acid starvation IMP 25263562
GO:0042149 cellular response to glucose starvation IMP 25263562
GO:0055114 oxidation-reduction process IEA --
GO:0071230 cellular response to amino acid stimulus IBA 21873635
genes like me logo Genes that share ontologies with SESN1: view

No data available for SIGNOR curated interactions for SESN1 Gene

Drugs & Compounds for SESN1 Gene

No Compound Related Data Available

Transcripts for SESN1 Gene

mRNA/cDNA for SESN1 Gene

3 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SESN1

Alternative Splicing Database (ASD) splice patterns (SP) for SESN1 Gene

No ASD Table

Relevant External Links for SESN1 Gene

GeneLoc Exon Structure for
SESN1

Expression for SESN1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SESN1 Gene

mRNA differential expression in normal tissues according to GTEx for SESN1 Gene

This gene is overexpressed in Muscle - Skeletal (x5.5).

Protein differential expression in normal tissues from HIPED for SESN1 Gene

This gene is overexpressed in Testis (35.9) and Serum (13.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SESN1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SESN1

SOURCE GeneReport for Unigene cluster for SESN1 Gene:

Hs.591336

mRNA Expression by UniProt/SwissProt for SESN1 Gene:

Q9Y6P5-SESN1_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for SESN1 Gene

  • Lung(4.5)
  • Nervous system(4.1)
  • Muscle(3.1)
  • Heart(2.6)
  • Intestine(2.6)
  • Skin(2.5)
  • Liver(2.4)
  • Spleen(2.4)
  • Kidney(2.3)
  • Blood(2.2)
  • Bone marrow(2.2)
  • Lymph node(2.1)
  • Pancreas(2)
genes like me logo Genes that share expression patterns with SESN1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SESN1 Gene

Orthologs for SESN1 Gene

This gene was present in the common ancestor of animals.

Orthologs for SESN1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SESN1 30 31
  • 99.76 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SESN1 30 31
  • 95.72 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SESN1 30 31
  • 93.28 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SESN1 31
  • 92 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Sesn1 30 17 31
  • 88.87 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Sesn1 30
  • 86.67 (n)
Oppossum
(Monodelphis domestica)
Mammalia SESN1 31
  • 85 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SESN1 30 31
  • 77.05 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SESN1 31
  • 80 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia sesn1 30
  • 76.34 (n)
African clawed frog
(Xenopus laevis)
Amphibia sesn1-A 30
Zebrafish
(Danio rerio)
Actinopterygii sesn1 30 31
  • 70.82 (n)
OneToOne
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10916 30
Fruit Fly
(Drosophila melanogaster)
Insecta Sesn 31
  • 41 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea sesn-1 31
  • 24 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.3472 31
  • 33 (a)
OneToMany
Species where no ortholog for SESN1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for SESN1 Gene

ENSEMBL:
Gene Tree for SESN1 (if available)
TreeFam:
Gene Tree for SESN1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SESN1: view image

Paralogs for SESN1 Gene

Paralogs for SESN1 Gene

(2) SIMAP similar genes for SESN1 Gene using alignment to 1 proteins:

  • SESN1_HUMAN

Pseudogenes.org Pseudogenes for SESN1 Gene

genes like me logo Genes that share paralogs with SESN1: view

Variants for SESN1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SESN1 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
rs2273668 - p.Leu44Ile

Additional dbSNP identifiers (rs#s) for SESN1 Gene

Structural Variations from Database of Genomic Variants (DGV) for SESN1 Gene

Variant ID Type Subtype PubMed ID
nsv1017230 CNV gain 25217958
nsv1117662 CNV deletion 24896259
nsv830768 CNV gain 17160897
nsv950492 CNV duplication 24416366

Variation tolerance for SESN1 Gene

Residual Variation Intolerance Score: 5.83% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.22; 69.96% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SESN1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SESN1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SESN1 Gene

Disorders for SESN1 Gene

MalaCards: The human disease database

(2) MalaCards diseases for SESN1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
endometrial adenosquamous carcinoma
  • adenosquamous carcinoma of endometrium
tuberous sclerosis 2
  • ts
- elite association - COSMIC cancer census association via MalaCards
Search SESN1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SESN1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with SESN1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SESN1 Gene

Publications for SESN1 Gene

  1. PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes. (PMID: 9926927) Velasco-Miguel S … Kley N (Oncogene 1999) 2 3 4 23
  2. PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse. (PMID: 12607115) Peeters H … Devriendt K (Human genetics 2003) 3 4 23
  3. Sestrin2 is a leucine sensor for the mTORC1 pathway. (PMID: 26449471) Wolfson RL … Sabatini DM (Science (New York, N.Y.) 2016) 3 4
  4. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. (PMID: 25263562) Chantranupong L … Sabatini DM (Cell reports 2014) 3 4
  5. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. (PMID: 23274085) Bae SH … Rhee SG (Cell metabolism 2013) 3 4

Products for SESN1 Gene

Sources for SESN1 Gene